A post hoc analysis of the phase 3 GATHER2 trial, presented at the 2026 American Society of Retina Specialists meeting in Montreal, provides additional evidence linking retinal structure and visual function in geographic atrophy (GA). Investigators found that ellipsoid zone (EZ) integrity and low-luminance deficit (LLD) moved in parallel, supporting their use as complementary markers of disease progression and treatment response.
Rachel A. Downes, MD, presented the finding on behalf of investigators from the Cleveland Clinic Cole Eye Institute. The analysis evaluated patients treated with avacincaptad pegol (Izervay; Astellas Pharma) who, after 12 months of monthly dosing, continued monthly treatment or switched to every-other-month dosing during the second year of GATHER2.
The work built on an earlier pooled analysis of the GATHER trials showing that eyes with greater baseline LLD also had greater EZ attenuation. “These seem to be eyes with more severe GA that did worse on both of these variables,” explained Dr. Downes. She noted that LLD, defined as the difference between best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA), measures “the number of letters that a patient loses when the luminance is turned down.”
Patients were divided into quartiles according to baseline LLD. The investigators assessed partial EZ attenuation, defined as the percentage of the macular cube with EZ-RPE thickness of 20 μm or less, and total EZ attenuation, defined as the percentage with EZ-RPE thickness of 0 μm. Baseline analyses showed that patients in the lowest LLD quartile had less partial or total EZ attenuation than those in the highest quartile, reinforcing the relationship between structural damage and visual function.
By month 18, both monthly and every-other-month avacincaptad pegol reduced progression of partial and total EZ attenuation compared with sham, with the largest differences observed among patients with the greatest baseline LLD. For partial EZ attenuation, reductions vs sham reached approximately 62% with monthly dosing and 67% with every-other-month dosing in the highest LLD quartile. For total EZ attenuation, the corresponding reductions were approximately 31% with either dosing schedule.
“The eyes that saw the greatest benefit were actually the eyes that had the worst baseline low-luminance deficit,” Dr. Downes said. “Patients who already were having a lot of difficulty seeing under low-luminance conditions saw the most benefit in terms of maintaining their EZ moving forward.”
Dr. Downes said analyses like these can help bridge structural imaging with patients’ visual experience. “We’re eager to understand the functional impact of complement inhibition and treatments for GA,” she said. “These types of exploratory analyses are hopefully going to be more and more useful as we obtain more data and help us understand the practical implications for our patients.”
The post hoc analysis was supported by a grant from Astellas Pharma. RP